I am a faculty member in the Hospital Medicine Unit at Boston University Medical Center who seeks the GEMSSTAR R03 Award under the auspices of the Society of Hospital Medicine which is sponsoring a companion T. Franklin Williams award. These awards will enable me to transition into an independent hospitalist investigator in aging research. The proposal, entitled "Older Adult Safety in Surgery (OASIS)" focuses on identifying optimal perioperative injury prevention strategies in older adults with a single and co-occurring comorbidities undergoing surgery by measuring their associated long term health related quality of life, survival, and costs using a computer disease simulation model. Medical injury is common after major surgery and disproportionately affects older adults with comorbidities. The proposal uses venous thromboembolism (VTE) prophylaxis after total hip and knee replacement as a first case example of a method which may be replicated for numerous other safety targets. The American College of Chest Physicians recommends exclusively high potency prophylaxis in this setting. High potency agents including fondaparinux and LMWH are highly effective in reducing the incidence of VTE but concerns about increased rates of bleeding with these regimens have slowed their widespread adoption especially in older adults. Selecting the optimal intervention to prevent medical injury usually involves balancing its risks, benefits, and costs. These have not been carefully studied for most procedures, particularly for older adults with comorbidities and co-occurring comorbidities. In this proposal, I will use computer disease simulation to integrate data from published randomized controlled trials about the efficacy of high potency prophylaxis, cohort data about the background risk of VTE, and cost from Medicare reimbursement statistics to project long term outcomes related to various prophylaxis strategies. Then, I will measure the relative risk of VTE and bleeding in subpopulations of older adults with prevalent comorbidities using regression analyses of Veterans Affairs data and project long term outcomes with the simulation model in these subpopulations. If the conclusions about the value of high potency prophylaxis changes in the subpopulations, the method outlined would represent a major innovation in the perioperative assessment of older adult surgical patient. PUBLIC HEALTH RELEVANCE: Choosing the appropriate VTE prophylaxis regimen given associated risks for older adults undergoing total joint replacement is one example of the difficult risk-benefit decisions that must be made by physicians and patients in the perioperative period. Understanding the relationship between comorbidities and risk of injury will be instrumental to determining the optimal prevention strategies for physicians, patients, and policy makers.